Core D: Neuropathology Core Project Summary/Abstract The UCI ADRC Neuropathology (NP) Core links clinical evaluations with definitive neuropathological diagnoses. Neuropathology remains the definitive method for diagnosing Alzheimer's disease (AD). The UCI ADRC cohorts consist of a longitudinal cohort, and two unique patient populations: adults with Down syndrome and individuals over 90 years of age ( 90+ ), representing cohorts at high risk of developing dementia. Down syndrome represents the single most prevalent cause of early-onset AD, whereas the 90+ cohort represents subjects with a high rate of conversion to dementia. Both cohorts provide unique opportunities to study the transition of `cognitively normal' to dementia. The overarching goal of the NP Core is to provide the infrastructure to support research on all three ADRC cohorts that aim to elucidate the underlying mechanisms that define normal aging, the transition to MCI, and the subsequent transition from MCI to AD/dementia. As part of its mission, the UCI NP Core disseminates well-characterized tissues, biospecimens and reagents to basic scientists at UCI and abroad to stimulate and facilitate research in AD and other age-associated neurodegenerative diseases. Using standardized methods for processing, the NP Core supports multi-center collaborative studies. Additionally, the NP Core seeks to innovate by establishing infrastructure to support novel technologies, techniques, and data collection to increase the value of the stored tissue and biospecimens. Lastly, the NP Core reports important AD research findings in collaboration with the Education Core. In order to achieve the goals of the NP Core, we propose seven specific aims: (1) Perform an accurate and timely autopsy of the ADRC cohorts (Longitudinal, Down syndrome, and 90+) and provide a standardized neuropathological report to the Data Management and Statistics Core for deposition with NACC, and to the Clinical Core for dissemination to the families of the deceased participants and their physicians; (2) Store, catalog, and disseminate brain tissue and biospecimens from ADRC subjects; (3) Store, catalog, and disseminate novel reagents made by UCI investigators; (4) Support and consult on ADRC projects, ADRC pilot studies, and studies on AD mechanisms by investigators funded by other means, including ADC collaborative projects; (5) Develop and establish new core functions to facilitate innovative research to study the transition of MCI to AD; (6) Participate in the public education of Chinese-Americans and others; (7) Train pathologists, neurologists, neurosurgeons, neuroscientists, neuropsychologists, and students on the neuropathological features of AD and other dementing disorders.